Many of the disease manifestations found in multiple myeloma and, in some cases, the ultimate cause of death relate to the production of "abnormal" antibody-like proteins that are deposited in the kidney and other organs throughout the body. Bence Jones proteins are the light chain component of the immunoglobulin molecule. Certain Bence Jones proteins are "malignant" in that they form toxic proteinaceous deposits in the form of renal tubular casts, nonfibrilar basement membrane deposits, and fibrilar amyloid deposits. Other Bence Jones proteins are "benign" in that they cause no obvious disease. An ability to determine in individual patients whether a Bence Jones protein is likely to produce disease and to understand the molecular mechanism(s) that account for this deposition will contribute to the development of therapeutic measures to prevent, arrest, and possibly to reverse light chain deposition. We have applied an in vitro chromatographic system to the study of the aggregation of Bence Jones proteins under physiological conditions. Our preliminary data lead us to believe that this system can be used diagnostically to discriminate benign from malignant Bence Jones proteins. Under conditions that reflect pH, osmotic, and urea concentration characteristics in the nephron, we have distinguished cast-forming light chains from those that do not have this property. We propose to optimize this experimental system and confirm for diagnostic purposes the correlation between chromatographically observed properties and the presence or absence of pathological characteristics expressed clinically. We will also use x-ray crystallographic techniques to help identify possible molecular bases for light chain disease. The availability of crystals from representative proteins will permit us to study the structural aspects of light chain aggregation.